Experiments evaluating the effects of arvin, exogenous fibrinogen, and thrombin on the metabolism of fibrinogen will be performed. The rabbit model will allow discrimination between changes in synthesis, catabolism, and ex-travascular pools. The prolonged hypofibrinogenemia that follows defibrino-genation by arvin will be evaluated. Studies of prothombin metabolism, during defibrinogenation by arvin, will be carried out in man. A clinical investigation is underway to determine the frequency of thrombocytopenia and other changes in blood coagulation that may be asso-ciated with the administration of heparin. an experimental model in rats also is being used to evaluate the effects of heparin. A double-blind, controlled study of the use of heparin for the treatment of disseminated intravascular coagulation is in progress. The potential pathophysiologic role of bacterial endotoxins in various disease states, including cyclic neutropenia, plague, and typhoid fever, will be evaluated. Additional characterization of the clottable protein, which forms the basis of the Limulus test for bacterial endotoxins, will be attempted. The effects of thrombin and heparin, on the invertebrate coagu-lation mechanism of Limulus, will be evaluated. The biological activity of radiolabeled endotoxin will be compared in different bioassay systems, prior to its utilization in various physiologic studies. BIBLIOGRAPHIC REFERENCES: Glew, R.H. and Levin, J. Failure to demonstrate circulating endotoxin in malaria. Proc. Soc. Exp. Biol. Med. 148:508, 1975. Som, P., Rhodes, B.A., and Bell, W.R. Radiolabeled streptokinase and urokinase and their comparative biodistribution. Thromb. Res. 6:247, 1975. Tomasulo, P.A., March, S.C., and Levin, J. Tritiation of endotoxin. Biochim. Biophys. Acta 400:399, 1975.